Adenosine A2A receptors facilitate 45Ca2+ uptake through class A calcium channels in rat hippocampal CA3 but not CA1 synaptosomes.
In the hippocampus, the neuromodulatory role of adenosine depends on a balance between inhibitory A1 responses and facilitatory A2A responses. Since the presynaptic effects of hippocampal inhibitory A1 adenosine receptors are mostly mediated by inhibition of Ca2+ channels, we now investigated whether presynaptic facilitatory A2A adenosine receptors would modulate calcium influx in the hippocampus. The mixed A1/A2 agonist, 2-chloroadenosine (CADO; 1 microM) inhibited veratridine (20 microM)-evoked 45Ca2+ influx into hippocampal synaptosomes of the CA1 or CA3 areas by 24.2 +/- 4.5% and 17.2 +/- 5.8%, respectively. In the presence of the A, antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 100 nM), the inhibitory effect of CADO (1 microM) on 45Ca2+ influx was prevented in CA1 synaptosomes, but was converted into a facilitatory effect (14.2 +/- 6.7%) in CA3 synaptosomes. The A2A agonist, CGS 21680 (3-30 nM) facilitated 45Ca2+ influx in CA3 synaptosomes, with a maximum increase of 22.9 +/- 3.9% at 10 nM, and was virtually devoid of effect in CA1 synaptosomes. This facilitatory effect of CGS 21680 (10 nM) in CA3 synaptosomes was prevented by the A2A antagonist 8-(3-chlorostyryl)caffeine (CSC; 200 nM), but not by the A1 antagonist, DPCPX (20 or 100 nM). The facilitatory effect of CGS 21680 on 45Ca2+ uptake by CA3 synaptosomes was prevented by the class A calcium channel blocker, omega-agatoxin-IVA (200 nM). These results indicate that presynaptic adenosine A2A receptors facilitate calcium influx in the CA3 but not the CA1 area of the rat hippocampus through activation of class A calcium channels.
Gonçalves
M L
ML
Laboratory of Pharmacology, Faculty of Pharmacy, University of Lisbon, Portugal.
Cunha
R A
RA
Ribeiro
J A
JA
D015762:2-Chloroadenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D002132:Calcium Radioisotopes / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010627:Phenethylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014970:Xanthines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D013111:Spider Venoms; D014970:Xanthines; D020867:omega-Agatoxin IVA; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D015762:2-Chloroadenosine; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; D014701:Veratridine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine